This study identifies the ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 module as a key pathway for quantitative resistance to gray leaf spot (GLS) in maize. The ZmWAKL gene, which encodes a cell-wall-associated receptor kinase-like protein, is the causative gene for the major quantitative disease resistance locus qRgls1. The ZmWAKL-Y protein, the resistance allele, self-associates and interacts with ZmWIK on the plasma membrane, leading to the phosphorylation of ZmBLK1 and subsequent activation of ZmRBOH4, which triggers a reactive oxygen species (ROS) burst. This pathway enables the plant to detect pathogen invasion, transmit immune signals, and activate defense responses, resulting in increased resistance to GLS. The study also reveals that ZmWAKL-Y interacts with ZmWIK to form a receptor complex that activates downstream signaling, with ZmWAKL-Y showing stronger phosphorylation activity than ZmWAKL-Q. ZmBLK1, a cytoplasmic kinase, is phosphorylated by ZmWAKL/Y and ZmWIK, and subsequently phosphorylates ZmRBOH4, which is crucial for ROS production and GLS resistance. The ZmRBOH4 gene, when knocked out, results in reduced GLS resistance. The study provides a comprehensive understanding of the molecular mechanisms underlying GLS resistance in maize, highlighting the importance of the ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 module in plant immunity. This discovery has significant implications for improving disease resistance in maize and other crops.This study identifies the ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 module as a key pathway for quantitative resistance to gray leaf spot (GLS) in maize. The ZmWAKL gene, which encodes a cell-wall-associated receptor kinase-like protein, is the causative gene for the major quantitative disease resistance locus qRgls1. The ZmWAKL-Y protein, the resistance allele, self-associates and interacts with ZmWIK on the plasma membrane, leading to the phosphorylation of ZmBLK1 and subsequent activation of ZmRBOH4, which triggers a reactive oxygen species (ROS) burst. This pathway enables the plant to detect pathogen invasion, transmit immune signals, and activate defense responses, resulting in increased resistance to GLS. The study also reveals that ZmWAKL-Y interacts with ZmWIK to form a receptor complex that activates downstream signaling, with ZmWAKL-Y showing stronger phosphorylation activity than ZmWAKL-Q. ZmBLK1, a cytoplasmic kinase, is phosphorylated by ZmWAKL/Y and ZmWIK, and subsequently phosphorylates ZmRBOH4, which is crucial for ROS production and GLS resistance. The ZmRBOH4 gene, when knocked out, results in reduced GLS resistance. The study provides a comprehensive understanding of the molecular mechanisms underlying GLS resistance in maize, highlighting the importance of the ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 module in plant immunity. This discovery has significant implications for improving disease resistance in maize and other crops.